title: Effects of sivelestat treatment on acute lung injury in paraquat-intoxicated rats.
abstract: Lung injury is the main cause of death in acute paraquat (PQ) intoxication. Sivelestat (SV), a neutrophil elastase inhibitor, is effective in reducing inflammation in acute lung injury. The aim of this study was to examine the effect of SV on acute lung injury in PQ-intoxicated rats. Seven-week-old male Sprague-Dawley rats were randomly assigned to four groups: (1) control group (group N; n = 5); (2) PQ + normal saline (group P; n = 6); (3) normal saline + SV (group S; n = 6) and (4) PQ + SV (group PS; n = 6). SV treatment (intraperitoneally [i.p.], 20 mg/kg) was performed 30 minutes after PQ injection (i.p., 100 mg/kg), and injections were continued every hour for a total of five doses. One hour after the last treatment, blood samples were obtained for analysis of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Lung sections were stained with hematoxylin--eosin for light microscopic analysis. Neutrophil infiltration score of group PS was significantly lower than that of group P (p < 0.05). But, other scores and total score had no significant differences. IL-6 of group PS did not differ, compared to group P. In addition, there were no differences among the four groups. TNF-α of group PS was reduced, in comparison to the level of group P. SV attenuated neutrophil infiltration in PQ-induced acute lung injury in rats. In addition, systemic inflammation was partially suppressed with SV treatment, suppressing TNF-α production. These results suggest that SV reduces paraquat-induced lung injury, at least partially, by inhibiting neutrophil infiltration and TNF-α secretion.
authors.affiliation: Department of Emergency Medicine, College of Medicine, Chungbuk National University , Cheongju , Korea .
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Kyung Hye
authors.initials: KH
authors.lastname: Park
authors.forename: Hoon
authors.initials: H
authors.lastname: Kim
authors.forename: Song Yi
authors.initials: SY
authors.lastname: Choi
mesh_terms: D055371:Acute Lung Injury; D000818:Animals; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006652:Histological Techniques; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C069195:sivelestat; D005998:Glycine